Enterocolitis, NecrotizingNCT06422988
Do Probiotics Reduce The Risk Of Severe Necrotising Enterocolitis (NEC) In Infants Born Before 32 Weeks Gestation?
An observational study of Enterocolitis, Necrotizing, run by Imperial College London at 1 site in United Kingdom.
Trial summary
Necrotising enterocolitis (NEC) is one of the leading causes of mortality and morbidity in very preterm infants. This study aims to determine whether NEC rates are different between infants who receive probiotics versus infants who do not receive probiotics. Read more about this study
- Who is it for?
- Ages Up to 32 weeks
- Conditions the study is for
- Enterocolitis, Necrotizing
- What is being tested?
- Probiotics
- How many people
- 48,000 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 30 May 2024to 30 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 32 weeks
- All sexes
- No healthy volunteers
- Child
Study population: Infants born very preterm i.e. before 32 weeks gestation
Who may be able to join
- Eligible infants must have been born at less than 32 weeks gestation and be cared for in a English or Welsh unit which contributes data to the National Neonatal Research Database (this includes all NHS neonatal units in England and Wales).
- Infants born in the period January 1st, 2016, to December 31st, 2022 (7 years) will be included.
Who cannot join
- They have missing data for any of: gestational age at birth, birth weight, year of birth and date of death (for those that died).
- Their NNRD record does not include details of their first admission or begins after Day 3 of life.
- The absolute value of their recorded birthweight for gestational age z score exceeds 4 or is missing.
- They die in the first two postnatal days of life.
- They have a major congenital abnormality
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Do Probiotics Reduce The Risk Of Severe Necrotising Enterocolitis (NEC) In Infants Born Before 32 Weeks Gestation? An Observational Study Using Routinely Collected Data.
Necrotising enterocolitis (NEC) is one of the leading causes of mortality and morbidity in very preterm infants. This study aims to determine whether NEC rates are different between infants who receive probiotics versus infants who do not receive probiotics. The study has a retrospective cohort design and will utilise routinely collected data from the UK National Neonatal Research Database (NNRD). The cohort will comprise all infants born before 32 weeks gestation and cared for in neonatal units in England and Wales between 2016 and 2022. A propensity score matched approach will be used to conduct two comparisons: i) the risk of necrotising enterocolitis (NEC) between who do and those who do not receive probiotics in the first 14 days of life ii) the risk of NEC between babies who receive the two most common probiotic products used in UK units, (Labinic and Proprems).
- Conditions
- Enterocolitis, Necrotizing
- Being tested
- Probiotics
- Keywords
- Probiotics
- Medical subject headings
- Enterocolitis, Necrotizing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbioticsDietary supplement
Also called Labinic, Proprems, Acidophillus, Bifidobacterium
Any exposure to probiotics in first 14 days of life
| Study group | Role | What they receive |
|---|---|---|
| Exposed to probiotics | Receipt of any probiotic in the first 14 days of life. Probiotics to include: Labinic, Proprems probiotic, Acidophillus, Bifidobacterium, Bio-kult, Infloran, LB2.
To address potential recording error, infants whose NNRD records show minimal (one day) of probiotic exposure will only be classed as exposed if they are cared for in a probiotic unit. Probiotic units are defined as:
* units who have confirmed that a guideline was in place to provide probiotics to infants born before 32 weeks gestation and that the guideline was in place at any point in the year that the infant was born OR
* units where more than 50% of the infants eligible to be part of the cohort received probiotics in the six months after the infant was born. Receives: Dietary Supplement: Probiotics | |
| No probiotic exposure | Did not receive any probiotic in the first 14 days of life. Receives: Dietary Supplement: Probiotics |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severe necrotising enterocolitis (NEC)
NEC confirmed at surgery or postmortem or listed as a cause of death
Measured: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Secondary outcomes (15)
Necrotising enterocolitis (NNAP definition)
NEC diagnosed at postmortem or NEC diagnosed during surgery or NEC diagnosed using clinical and radiographic features (where the infant has at least one clinical feature (bilious gastric aspirate or emesis, abdominal distension, occult, gross blood in stool) and at least one radiographic feature (pneumatosis, hepato-biliary gas, pneumoperitoneum)).
Measured: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Pragmatically defined NEC
Infants who had a recorded diagnosis of necrotising enterocolitis and received at least 5 consecutive days of antibiotics whilst also nil by mouth
Measured: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Late onset sepsis
HQIP NNAP case definition
Measured: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Pragmatically defined late onset sepsis
Growth of any organisms that appear in the NNAP lists of "Clearly pathogenic organisms" and "Other organisms"
Measured: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Survival to discharge home
Measured: On date of discharge from final neonatal unit, assessed up to 24 months
Survival without severe NEC or late onset sepsis (LOS)
LOS is defined according to the Healthcare Quality Improvement Partnership (HQIP) National Neonatal Audit Programme (NNAP) case definition i.e. blood stream or cerebrospinal fluid confirmed pure growth in culture after first three days of life
Measured: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Survival without any NEC
NEC is defined as per the NNAP definition
Measured: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Brain injury
Either left or right grade 3 or higher intra-ventricular haemorrhage or cystic periventricular leukomalacia
Measured: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Treated retinopathy of prematurity
Defined as cryotherapy, laser therapy or injection of anti-vascular endothelial growth factor therapy for ROP in either or both eyes
Measured: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Stage of retinopathy of prematurity
Measured: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Bronchopulmonary dysplasia
Defined as any respiratory or ventilatory support or supplemental oxygen at 36 weeks postmenstrual age
Measured: 36 weeks postmenstrual age
Severe bronchopulmonary dysplasia
Defined as ventilation via endotracheal tube or trachestomy, and excluding non-invasive support or CPAP, at 36 weeks postmenstrual age
Measured: 36 weeks postmenstrual age
Length of stay
Number of days between first neonatal unit admission and final neonatal unit discharge for surviving infants
Measured: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Time to full feeds
Defined as the number of days until an infant is recorded as not requiring any parenteral nutrition or fluid (i.e. no parenteral nutrition or intravenous dextrose)
Measured: Before discharge from final neonatal unit
Growth
Weight for post-menstrual age standard deviation score
Measured: 36 weeks corrected gestational age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2024
- Study start30 May 2024
- Primary completion30 Jul 2025 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Enterocolitis, NecrotizingStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 48,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- University of Nottingham, Newcastle University, Queen Mary University of London
- Responsible party
- Principal investigator, Cheryl Battersby, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06422988
- Sponsor's protocol ID
- IRAS323099
- Status last verified
- May 2025
- First submitted
- 24 Apr 2024
- Last updated
- 7 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Study protocol available now. Analysis code will be available after publication of results.
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Do Probiotics Reduce The Risk Of Severe Necrotising Enterocolitis (NEC) In Infants Born Before 32 Weeks Gestation? An Observational Study Using Routinely Collected Data.
- ClinicalTrials.gov ID
- NCT06422988
- Acronym / sponsor ID
- IRAS323099
- Conditions
- Enterocolitis, Necrotizing
- Keywords
- Probiotics
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 48,000 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- University of Nottingham, Newcastle University, Queen Mary University of London
- Study start
- 30 May 2024 (actual)
- Primary completion
- 30 Jul 2025 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 21 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Necrotising enterocolitis (NEC) is one of the leading causes of mortality and morbidity in very preterm infants. This study aims to determine whether NEC rates are different between infants who receive probiotics versus infants who do not receive probiotics. The study has a retrospective cohort design and will utilise routinely collected data from the UK National Neonatal Research Database (NNRD). The cohort will comprise all infants born before 32 weeks gestation and cared for in neonatal units in England and Wales between 2016 and 2022. A propensity score matched approach will be used to conduct two comparisons: i) the risk of necrotising enterocolitis (NEC) between who do and those who do not receive probiotics in the first 14 days of life ii) the risk of NEC between babies who receive the two most common probiotic products used in UK units, (Labinic and Proprems).
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exposed to probiotics | – | Dietary Supplement: ProbioticsReceipt of any probiotic in the first 14 days of life. Probiotics to include: Labinic, Proprems probiotic, Acidophillus, Bifidobacterium, Bio-kult, Infloran, LB2. To address potential recording error, infants whose NNRD records show minimal (one day) of probiotic exposure will only be classed as exposed if they are cared for in a probiotic unit. Probiotic units are defined as: * units who have confirmed that a guideline was in place to provide probiotics to infants born before 32 weeks gestation and that the guideline was in place at any point in the year that the infant was born OR * units where more than 50% of the infants eligible to be part of the cohort received probiotics in the six months after the infant was born. |
| No probiotic exposure | – | Dietary Supplement: ProbioticsDid not receive any probiotic in the first 14 days of life. |
Who may qualify
- Ages
- Up to 32 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Infants born very preterm i.e. before 32 weeks gestation
Key inclusion criteria (2 listed)
- Eligible infants must have been born at less than 32 weeks gestation and be cared for in a English or Welsh unit which contributes data to the National Neonatal Research Database (this includes all NHS neonatal units in England and Wales).
- Infants born in the period January 1st, 2016, to December 31st, 2022 (7 years) will be included.
Key exclusion criteria (5 listed)
- They have missing data for any of: gestational age at birth, birth weight, year of birth and date of death (for those that died).
- Their NNRD record does not include details of their first admission or begins after Day 3 of life.
- The absolute value of their recorded birthweight for gestational age z score exceeds 4 or is missing.
- They die in the first two postnatal days of life.
- They have a major congenital abnormality
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProbioticsAlso: Labinic, Proprems, Acidophillus, BifidobacteriumAny exposure to probiotics in first 14 days of life | Dietary supplement | Exposed to probiotics, No probiotic exposure |
Primary outcome
Severe necrotising enterocolitis (NEC)
Time frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
NEC confirmed at surgery or postmortem or listed as a cause of death
15 secondary outcomes
Necrotising enterocolitis (NNAP definition)
Time frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Pragmatically defined NEC
Time frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Late onset sepsis
Time frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Pragmatically defined late onset sepsis
Time frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Survival to discharge home
Time frame: On date of discharge from final neonatal unit, assessed up to 24 months
Survival without severe NEC or late onset sepsis (LOS)
Time frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Survival without any NEC
Time frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Brain injury
Time frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Treated retinopathy of prematurity
Time frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Stage of retinopathy of prematurity
Time frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Bronchopulmonary dysplasia
Time frame: 36 weeks postmenstrual age
Severe bronchopulmonary dysplasia
Time frame: 36 weeks postmenstrual age
Length of stay
Time frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Time to full feeds
Time frame: Before discharge from final neonatal unit
Growth
Time frame: 36 weeks corrected gestational age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2025.
- Individual participant dataSharing planned: Undecided. Study protocol available now. Analysis code will be available after publication of results.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Enterocolitis, Necrotizing, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 7 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Severe necrotising enterocolitis (NEC) (time frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2025.